Naringenin attenuates endoplasmic reticulum stress, reduces apoptosis, and improves functional recovery in experimental traumatic brain injury

• Published in: Brain research 2021-10, Vol.1769, p.147591-147591, Article 147591
• Main Authors: Deng, Chulei, Yi, Renxin, Fei, Maoxing, Li, Tao, Han, Yanling, Wang, Handong
• Format: Article
• Language: English
• Subjects: Endoplasmic reticulum stress; Naringenin; Oxidative stress; Traumatic brain injury
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2021.147591

[Display omitted] •TBI-induced ER structure transformation in TEM.•Naringenin ameliorated secondary brain injury in mice with traumatic brain injury.•Naringenin’s neuroprotective effects may include ER stress attenuation. Traumatic brain injury (TBI) is a significant cause of disability and death worldwide. Accumulating evidence suggests that endoplasmic reticulum (ER) stress would be an important component in the pathogenesis of TBI. Although the neuroprotective effects of naringenin, a natural flavonoid isolated from citrus plants, have been confirmed in several neurological diseases, its mechanism of action in TBI needs further investigation. In ICR mice, we found that TBI induced elevated expression of ER stress marker proteins, including 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) in the perilesional cortex, which peaked at 7 days and 3 days after TBI, respectively. The induction of ER stress-related proteins partly coincided with ER architectural changes at 3 days post-TBI, indicating ER stress activation in our TBI model. Our results also revealed that continuous naringenin administration ameliorated neurological dysfunction, cerebral edema, plasmalemma permeability, and neuron cell loss at day 3 after TBI. Further, Naringenin suppressed TBI-induced activation of the ER stress pathway (p-eIF2α, ATF4, and CHOP), oxidative stress and apoptosis on day 3 after TBI. In summary, our data suggest that naringenin could ameliorate TBI-induced secondary brain injury by pleiotropic effects, including ER stress attenuation.